sinaror7 Corticosteroids
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Corticosteroids
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Corticosteroids
Mechanism of action
D enter cells where they combine with steroid receptors in cytoplasm
1 combination enters nucleus where it controls synthesis of protein, including enzymes that
regulate vital cell activities over a wide range of metabolic functions including all aspects
of inflammation
D formation of a protein that inhibits the enzyme phospholipase A which is needed to allow
the supply of arachidonic acid. Latter is essential for the formation of inflammatory
mediators
D also act on cell membranes to alter ion permeability
1D also modify the production of neurohormones
Actions
Important to distinguish between physiological effects (replacement therapy) and
pharmacological effects (occur at higher doses)
Mineralocorticoid
1 Na retention by renal tubule
increased K excretion in urine
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Glucocorticoid
1D CHO metabolism: increased gluconeogenesis, @ peripheral glucose uptake may be
decreased with resultant hyperglycaemia @ glycosuria
1 protein metabolism: anabolism is decreased but catabolism continues unabated or is
increased resulting in negative N balance and muscle wasting. Osteoporosis occurs,
growth slows in children, skin atrophies (together with increased capillary fragility leads
to bruising and striae), healing and fibrosis delayed
1 fat deposition: increased on shoulders, face and abdomen
1D inflammatory response depressed
D allergic response depressed
1 antibody production reduced by large doses
Di lymphoid tissue reduced (including leukaemic lymphocytes)
Di decreased eosinophils
Di renal urate excretion increased
1 euphoria or psychotic states may occur. ? due to CNS electrolyte changes
D anti-vitamin D action
1 reduction of hypercalcaemia (chiefly where this is due to increased absorption from gut:
vit D intoxication, sarcoidosis)
1D increased urinary Ca excretion. Renal stones may form
DI growth reduction where new cells are being added (eg in children) but not where they are
replacing cells as in adult tissues
1 suppression of HPA axis. NB steroid suppressed adrenal continues to secrete aldosterone
Normal daily secretion of hydrocortisone is 10-30 mg. Exogenous daily dose that completely
suppresses cortex is 40-80 mg (or prednisolone 10-20 mg).
Individual steroids
Relative potencies | Glucocorticoid | Mineralocorticoid
Hydrocortisone 1 1
Cortisol 1.25 1
Prednisolone 4 0.8
Methylprednisotone | 5 minimal
Dexamethasone 30 minimal
Fludrocortisone 15 150
I prednisolone is standard choice for anti-inflammatory therapy. Can be given orally or IM
1 methylprednisolone used for IV pulsed therapy
1 dexamethasone longer acting.
1 fludrocortisone used to replace aldosterone where the adrenal cortex has been destroyed
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1 beclomethasone and budesonide used by inhalation for asthma. About 90% of inhalation
dose is swallowed and inactivated by first-pass hepatic metabolism (steroids listed above
are protected from this by protein binding). The rest, which is absorbed from the mouth
and lungs gives very low systemic plasma concentrations. Although risk of HPA axis
suppression is very low it can happen.
Pharmacokinetics
Administration: PO/IM/IV/intra-articular/topical/inhaled. Absorption after oral administration
is rapid. Maximum biological effect seen after 2-8 h
Distribution: high plasma protein binding (95% in case of hydrocortisone) to transcortin and
when this is saturated to albumin (80% in the case of hydrocortisone). Concentration of
transcortin is increased by oestrogens (eg pregnancy, oral contraceptives). In patients with very
low serum albumin doses should be reduced due to reduced binding capacity
Elimination: hepatic and renal.ty 2 of most steroids 1-3 h. Prolonged in renal and hepatic
disease and shortened by hepatic enzyme induction to an extent that may be clinically
important.
Adverse effects
In general serious unwanted effects are unlikely if daily dose is < 50 mg hydrocortisone or 10mg
of prednisolone or equivalent
D iatrogenic Cushings
D avascular necrosis of bone
1 depression and psychosis
1D peptic ulceration
1 others include cataract (chronic use), glaucoma (prolonged use of eye drops), raised ICP
and convulsions, blood hypercoagulability, menstrual disorders, fever
1 immunosuppression
1 HPA axis suppression: dependent on steroid used, dose, duration of administration and
time of administration. Single morning dose of <20mg prednisolone does not usually cause
suppression while 5mg in evening suppresses early morning activation of HPA axis
Use in pregnancy
Di teratogenic in animals
1 ? relationship between high dose steroids and cleft palate and other fetal abnormalities
D adrenal insufficiency due to HPA axis suppression in newborn only occurs with high
maternal doses
1 keep doses as low as possible in pregnancy
1D avoid fluorinated steroids (eg dexamethasone) as they are more teratogenic in animals
Treatment of intercurrent illness
1 maximum stress-induced output of cortisol is 200-300 mg/day
Fipsshwenw ic curk eduhiwebSeoricosterids him a4sinaror7 Corticosteroids
1D production following surgery tends to be much less. Based on normal cortisol production
rates the recommended daily doses of hydrocortisone equivalent for different categories
of surgery are:
Daily dose Duration
Minor (eg hernia repair) 25 mg 1 day
Intermediate (eg cholecystectomy, 50-75 mg 2 days
colectomy, joint replacement)
Major (eg oesophagectomy, cardiac 100-150 mg 2-3 days
surgery requiring CPB)
If the patients maintenance dose exceeds recommended dose to cover surgical stress there is
no evidence that any dose alteration is necessary and patient should continue to receive
maintenance dose over the perioperative period.
In the case of perioperative complications continued glucocorticoid administration consistent
with the postoperative stress response is appropriate
Further reading
Laurence DR, Bennett PN. Clinical Pharmacology, 7" ed, 1992
Chin R, Eagerton DC, Salem M. Corticosteroids. In Chernow B (ed). The pharmacological
approach to the critically ill patient, 3" ed, 1994
@ Charles Gomersall December 1999
‘@Chares Gomersal, April, 2014 ures otherwise stated. Th autor, editor and The Chinese Usivesty of Hong Kong take no responsibility for any adverse event
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